Interleukin-26, preferentially produced by T H 17 lymphocytes, regulates CNS barrier function.

Autor: Broux B; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Zandee S; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Gowing E; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Charabati M; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Lécuyer MA; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Tastet O; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Hachehouche L; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Bourbonnière L; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Ouimet JP; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Lemaitre F; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Larouche S; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Cayrol R; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Bouthillier A; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Moumdjian R; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Lahav B; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Poirier J; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Duquette P; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Arbour N; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Peelen E; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada., Prat A; From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada. a.prat@umontreal.ca.
Jazyk: angličtina
Zdroj: Neurology(R) neuroimmunology & neuroinflammation [Neurol Neuroimmunol Neuroinflamm] 2020 Aug 11; Vol. 7 (6). Date of Electronic Publication: 2020 Aug 11 (Print Publication: 2020).
DOI: 10.1212/NXI.0000000000000870
Abstrakt: Objective: To investigate the involvement of interleukin (IL)-26 in neuroinflammatory processes in multiple sclerosis (MS), in particular in blood-brain barrier (BBB) integrity.
Methods: Expression of IL-26 was measured in serum, CSF, in vitro differentiated T helper (T H ) cell subsets, and postmortem brain tissue of patients with MS and controls by ELISA, quantitative PCR, and immunohistochemistry. Primary human and mouse BBB endothelial cells (ECs) were treated with IL-26 in vitro and assessed for BBB integrity. RNA sequencing was performed on IL-26-treated human BBB ECs. Myelin oligodendrocyte glycoprotein 35-55 experimental autoimmune encephalomyelitis (EAE) mice were injected IP with IL-26. BBB leakage and immune cell infiltration were assessed in the CNS of these mice using immunohistochemistry and flow cytometry.
Results: IL-26 expression was induced in T H lymphocytes by T H 17-inducing cytokines and was upregulated in the blood and CSF of patients with MS. CD4 + IL-26 + T lymphocytes were found in perivascular infiltrates in MS brain lesions, and both receptor chains for IL-26 (IL-10R2 and IL-20R1) were detected on BBB ECs in vitro and in situ. In contrast to IL-17 and IL-22, IL-26 promoted integrity and reduced permeability of BBB ECs in vitro and in vivo. In EAE, IL-26 reduced disease severity and proinflammatory lymphocyte infiltration into the CNS, while increasing infiltration of Tregs.
Conclusions: Our study demonstrates that although IL-26 is preferentially expressed by T H 17 lymphocytes, it promotes BBB integrity in vitro and in vivo and is protective in chronic EAE, highlighting the functional diversity of cytokines produced by T H 17 lymphocytes.
(Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze: MEDLINE